Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

ObjectiveTo generate cynomolgus and rhesus monkey models carrying the Booroola fecundity (FecB) variant of bone morphogenetic protein receptor type 1B (BMPR1B) gene (designated BMPR1B^FecB) using adenine base edit technology and to explore genetic improvement strategies for enhancing the reproductive performance of laboratory macaques. MethodsFour single-guide RNAs (sgRNAs) were designed to target the BMPR1B c.746A>G locus in cynomolgus and rhesus monkeys. The sgRNAs were combined with the ABE8e-SpRY base editor, and the resulting editing complexes were microinjected into zygotes of both macaque species. Following in vitro culture of the injected embryos, nested PCR amplification was performed to detect the base-editing efficiency at the target site to screen for highly efficient sgRNAs. Subsequently, normally developing gene-edited embryos were transferred into the oviducts of surrogates. Seven days after birth, ear skin or peripheral blood samples were collected from the newborn monkeys for genotyping and mosaicism analysis, and the growth, development, and health status of the gene-edited monkeys were monitored. ResultsAmong the four candidate sgRNAs, sgRNA4 was identified as achieving 100% editing efficiency at the c.746A>G site. A total of 17 live monkey offspring were obtained via embryo transfer, including 8 cynomolgus monkeys and 9 rhesus monkeys. Genotyping results showed that all 8 newborn cynomolgus monkeys carried the c.746A>G point mutation, with an editing efficiency of 100% (8/8), of which 37.50% (3/8) were mosaics. Among the 9 newborn rhesus monkeys, 8 individuals carried the c.746A>G mutation, with an editing efficiency of 88.89% (8/9), of which 75.00% (6/8) were mosaics. ConclusionThe ABE8e-SpRY base-editing system enables precise editing at the c.746A>G (p.Q249R) locus of the BMPR1B gene in both cynomolgus and rhesus monkey embryos, resulting in the successful establishment of laboratory monkey models carrying the BMPR1B^FecB variant. These models provide a valuable foundation for future studies of the regulatory role of the BMPR1B^FecB variant in reproductive performance at the non‑human primate level, as well as for exploring genetic improvement strategies to enhance reproductive performance in laboratory monkeys.

Objective: To explore the therapeutic effects of different surgical methods for temporomandibular joint disc reduction and anchoring surgery, providing reference for optimizing this surgical procedure. Method: The study was approved by the hospital ethics committee. 173 patients (195 joints) who underwent temporomandibular joint disc repositioning and anchoring surgery were selected for retrospective analysis. Patients were categorized into groups A (traditional preauricular incision-scalpel/tissue scissors anterior attachment release), 35 patients (40 joints), B (traditional preauricular incision-plasma bipolar radiofrequency electrode anterior attachment release), 42 patients (46 joints), C (revised tragus incision - scalpel/tissue scissors anterior attachment release), 50 patients (58 joints), and D (revised tragus incision-plasma bipolar radiofrequency electrode anterior attachment release), 46 patients (51 joints). After a 6-month postoperative follow-up, the differences in maximum mouth opening (MMO), visual analogue scale (VAS), effective rate of joint disc reduction, incidence of preauricular numbness, obvious scars among patients in each group at 1, 3, and 6 months were compared postoperatively. Results: After surgery, the MMO of all four groups of patients initially shrunk and then gradually increased compared to before surgery. At the 1-month follow-up after surgery, the plasma bipolar radiofrequency release (B+D) group had a smaller impact on the patient’s MMO compared to the surgical knife/tissue scissors release (A+C) group (P < 0.05). Postoperative VAS scores for all four groups showed a gradual decrease from pre-operative levels, with the (B+D) group scoring significantly lower in the first month post-surgery compared to the (A+C) group (P < 0.05). Six months post-surgery, the rate of joint disc reduction of the four groups were higher than 95%, with no significant differences observed between the groups (P > 0.05). Patients in the revised tragus incision (C+D) group experienced a lower rate of preauricular numbness compared to those in the traditional preauricular incision (A+B) group (4.59% vs. 12.79%, P < 0.05), The incidence of obvious scars in the (C+D) group was significantly lower than that in the (A+B) group (3.67% vs. 23.26%, P < 0.05). Conclusion The revised tragus incision is superior to traditional preauricular incision in terms of protecting the auriculotemporal nerve and the scars were more inconspicuous. Further, the plasma bipolar radiofrequency electrode is superior to the scalpel/tissue scissors in terms of mouth opening recovery and pain control. For temporomandibular joint disc reduction and anchoring surgery, a modified tragus incision combined with plasma bipolar radiofrequency electrode to release the anterior attachment of the joint disc can be recommended as a surgical option.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective To explore the application value of serological markers in the screening of malignant tumor bone metastasis.Methods A total of 113 patients with malignant tumor bone metastasis first diag-nosed in a hospital from June 2023 to February 2024 were selected as case group.Another 80 patients with malignant tumor without bone metastasis diagnosed in the same period were selected as the control group.The levels of serological markers[serum calcium(Ca),parathyroid hormone(PTH),Ca/PTH,procollagen type 1 amino-terminal propeptide(P1NP),beta-C-terminal telopeptide of type 1 collagen(β-CTX)and N-terminal mid-fragment of osteocalcin]were compared between the two groups.Receiver operating characteristic(ROC)curves were plotted to analyze the value of serological markers in screening for bone metastases of lung canc-er,prostate cancer and breast cancer.Multivariate Logistic regression was used to analyze the related factors of malignant tumor bone metastasis.Results The levels of Ca,Ca/PTH,β-CTX and P1NP in case group were significantly higher than those in control group,while PTH in case group was lower than that in control group,with statistical significance(P<0.05).ROC curve results showed that Ca,PTH,Ca/PTH,P1NP and β-CTX had high efficacy in screening malignant tumor bone metastases,and the area under the curve(AUC)was 0.718,0.699,0.712,0.648 and 0.593,respectively.Multivariate Logistic regression analysis showed that Ca/PTH and P1NP were the influencing factors of bone metastasis in malignant tumor(OR=5.036,1.013,P<0.05).The AUC of Ca,PTH and Ca/PTH screening for bone metastasis of lung cancer were 0.781,0.652 and 0.669,respectively.The AUC of β-CTX and P1NP screening for bone metastasis of prostate cancer were 0.800 and 0.815 respectively.The AUC of Ca and P1NP screening for breast cancer with bone metastasis was 0.751 and 0.794,respectively.Conclusion Serological markers(Ca,PTH,Ca/PTH,P1NP and β-CTX)are valuable in screening for malignant tumor bone metastasis.

Bone metastasis is a serious complication in the course of malignant tumors and has a poor prog-nosis.The incidence of breast cancer,prostate cancer and lung cancer is the highest.A highly sensitive and highly specific test method for the early diagnosis of malignant bone metastases of these tumors,which is es-sential for reducing the incidence of bone-related events and improving the prognosis of patients with malig-nant tumors,is urgently needed.At present,the diagnosis of bone metastasis in patients with malignant tumors mainly relies on imaging.However,due to limitations in the development of imaging technology,its clinical use is still limited by sensitivity,cost-effectiveness,availability,and others.Close clinical follow-up and monitoring of patients diagnosed with malignant tumors are essential for effective patient management.Based on the current literature,this review aims to summarize the early diagnosis and detection methods for bone metastases in breast cancer,prostate cancer and lung cancer,including imaging techniques,pathology,bio-chemistry and molecular methods,and to review the development trends of future diagnostic techniques.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

Objective:To characterize the bacterial communities present in the root apical regions associated with persistent apical periodontitis(PAP).Methods:6 periapical lesion samples were collected from the teeth with PAP.DNA was extracted and ampli-fied by PCR based on the V3-V4 region of 16S rRNA gene.Illumina high throughput sequencing was applied to achieve the infor-mation of microbial community.Results:In total,447 OTUs were assigned,the average number of OTUs for the samples was 164.83±56.24.The phyla Firmicutes,Actinobacteria,Bacteroidetes,Proteobacteria and Fusobacteria were detected with high rela-tive abundances in all samples.At the genus level,the prevalent bacterial genera were Bifidobacterium,Streptococcus,Bacillus,En-terococcus and Porphyromonas,which were abundantly detected in all samples.The 6 samples were divided into 2 groups by hierar-chical cluster analysis.Prevotella and Treponema were abundant in group A,Bifidobacterium,Streptococcus and Enterococcus were abundant in group B.Conclusion:The bacterial profiles of root apical region of the teeth with PAP can be illustrated that diverse bacterial communities located in apical lesions.The bacterial composition of PAP can be divided into 2 microbial pattern and the re-lationship between different bacteria may guide new strategies to control infection.

OBJECTIVE: To explore the feasibility of using biomechanical indicators as supplementary evaluation to the Musculoskeletal Tumor Society Scoring System (MSTS) for amputee patients. METHODS: Twenty-four patients who underwent hemipelvectomy between September 2018 and January 2025 were enrolled. There were 15 males and 9 females with an average age of 61.4 years (range, 45-76 years). Participants performed gait tests at self-selected speeds using three assistive devices (prosthesis, single crutch, and double crutches). Motion data were analyzed using a customized OpenSim model. Biomechanical indicators of the intact limb exhibiting common characteristics were screened through correlation and sensitivity analyses. Test-retest reliability [interclass correlation coefficient (ICC)] of selected parameters was assessed to evaluate their potential as MSTS score supplements. RESULTS: All biomechanical indicators showed significant positive correlations with MSTS scores across assistive devices ( P<0.05). Seven indicators demonstrated |Pearson correlation coefficients|>0.8, including walking speed, maximum hip angle, maximum hip moment, peak hip flexion moment, peak hip extension moment, hip flexion impulse, and hip extension impulse. Among these, maximum hip moment, hip flexion impulse, and hip extension impulse exhibited significant between-group differences in adjacent MSTS levels ( P<0.05), indicating high sensitivity, along with excellent test-retest reliability (ICC>0.74, P<0.01). CONCLUSION Biomechanical indicators statistically qualify as potential supplements to MSTS scoring. Maximum hip moment, hip flexion impulse, and hip extension impulse demonstrate particularly high sensitivity to MSTS score variations.
Humans ; Male ; Middle Aged ; Female ; Aged ; Biomechanical Phenomena ; Amputees/rehabilitation* ; Feasibility Studies ; Artificial Limbs ; Reproducibility of Results ; Amputation, Surgical ; Crutches ; Gait